Possible roles of sestrin2 in multiple sclerosis and its relationships with clinical outcomes / Possíveis papéis da sestrina2 na esclerose múltipla e suas relações com resultados clínicos

ABSTRACT Background: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. Objective: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. Methods: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. Results: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. Conclusions: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

RESUMO Antecedentes: Caracterizada por desmielinização, inflamação e dano axonal, a esclerose múltipla (EM) é uma das doenças mais comuns do sistema nervoso central liderada pelo sistema imunológico. Há uma necessidade urgente e óbvia de biomarcadores para o diagnóstico e acompanhamento da EM. Objetivo: Investigar os níveis séricos de sestrina2 (SESN2), uma proteína que responde ao estresse agudo, em pacientes com EM. Métodos: Foram incluídos 85 participantes, 40 pacientes com diagnóstico prévio de EM recorrente-remitente e 45 controles saudáveis. Os parâmetros do SESN2 sérico foram investigados em amostras de sangue coletadas de cada participante nos grupos de paciente e controle. Resultados: os níveis de SESN2 foram significativamente mais baixos em pacientes com EM do que em controles (z: -3,06; p=0,002). Na análise ROC do SESN2, o nível preditivo para MS foi 2,36 ng/mL [sensibilidade, 72,50%; especificidade, 55,56%; p=0,002; área sob a curva (AUC)=0,693]. Para o valor de corte em ambos os grupos, SESN2 foi um preditor independente para MS [Exp (B)=3,977, intervalo de confiança de 95% (95%CI) 1,507-10,494; p=0,013]. Conclusões: A expressão diminuída de SESN2 pode desempenhar um papel na patogênese da EM, e SESN2 poderia ser usado como um biomarcador para EM e como agente imunoterapêutico para o tratamento de EM.

Serum levels of irisin and nesfatin-1 in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. OBJECTIVE: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). METHODS: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. RESULTS: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. CONCLUSION: The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.

Possible roles of sestrin2 in multiple sclerosis and its relationships with clinical outcomes.

BACKGROUND: Characterized by demyelination, inflammation and axonal damage, multiple sclerosis (MS) is one of the most common disorders of central nervous system led by the immune system. There is an urgent and obvious need for biomarkers for the diagnosis and follow-up of MS. OBJECTIVE: To investigate serum levels of sestrin2 (SESN2), a protein that responds to acute stress, in MS patients. METHODS: A total of 85 participants, 40 patients diagnosed previously with relapsing-remitting MS and 45 healthy controls, were included. Serum SESN2 parameters were investigated in blood samples drawn from each participant in the patient and control groups. RESULTS: SESN2 levels were significantly lower in MS patients than in controls (z: -3.06; p=0.002). In the ROC analysis of SESN2, the predictive level for MS was 2.36 ng/mL [sensitivity, 72.50%; specificity, 55.56%; p=0.002; area under the curve (AUC)=0.693]. For the cut-off value in both groups, SESN2 was an independent predictor for MS [Exp (B)=3.977, 95% confidence interval (95%CI) 1.507-10.494 and p=0.013]. CONCLUSIONS: The decreased expression of SESN2 may play a role in MS pathogenesis, and SESN2 could be used as a biomarker for MS and as immunotherapeutic agent to treat MS.

Serum levels of irisin and nesfatin-1 in multiple sclerosis / Níveis séricos de irisina e nesfatin-1 na esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. Objective: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). Methods: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. Results: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p<0.001; z: -4.79, p<0.001, respectively) The cut-off level of irisin is 10.390 (ng/mL) (sensitivity: 84.1%, specificity: 71.4%, AUC: 0.800), and the cut-off level of nestatin-1 is 7.155 (ng/mL) (sensitivity: 68.2%, specificity: 64.3%, AUC: 0.739) in the ROC analysis. For these cut-off levels in the case-control groups, the lower irisin and nesfatin-1 levels are the independent variables for MS patients (OR 9.723, 95%CI 2.884-32.785, p<0.001; OR 3.992, 95%CI 1.336-11.928, p<0.001) respectively. Conclusion: The present study revealed lower irisin and nesfatin-1 levels in patients with RRMS. These findings suggest that the decreased levels of irisin and nesfatin-1 peptides may contribute to MS pathogenesis such as inflammation, oxidative stress, and apoptosis in MS, leading to demyelination, axonal damage with neuronal loss, and gliosis.

RESUMO Antecedentes: A esclerose múltipla (EM) é uma doença neurológica crônica autoimune inflamatória e neurodegenerativa. Atualmente, não há biomarcadores séricos eficazes para verificar o diagnóstico de EM, para avaliar o prognóstico da doença e avaliar a resposta ao tratamento de EM. Objetivo: O presente estudo é uma avaliação preliminar dos níveis séricos de irisina e nesfatina-1 em pacientes com EM recorrente-remitente (EMRR). Métodos: Um total de 86 participantes, 42 pacientes com diagnóstico de EMRR e 44 controles saudáveis, foram incluídos no estudo. Os parâmetros séricos de irisina e nesfatina-1 dos pacientes e membros do grupo controle foram analisados. Resultados: Os níveis de irisina e nesfatina-1 dos pacientes com EMRR foram significativamente mais baixos do que os dos controles (z: -3,82, p <0,001; z: -4,79, p <0,001, respectivamente). O nível de corte de irisina é 10,390 (ng/mL) (sensibilidade: 84,1%, especificidade: 71,4%, AUC: 0,800), e o nível de corte de nestatina-1 é 7,155 (ng/mL) (sensibilidade: 68,2%, especificidade: 64,3%, AUC: 0,739) na análise ROC. Para esses níveis de corte nos grupos de caso-controle, os níveis mais baixos de irisina e nesfatina-1 são as variáveis independentes para pacientes com EM (OR 9,723, IC95% 2,884-32,785, p <0,001; OR 3,992, IC95% 1,336-11,928, p <0,001) respectivamente. Conclusão: O presente estudo revelou níveis mais baixos de irisina e nesfatina-1 em pacientes com EMRR. Esses achados sugerem que os níveis diminuídos de peptídeos irisina e nesfatina-1 podem contribuir para a patogênese da EM, como inflamação, estresse oxidativo e apoptose na EM, levando à desmielinização, dano axonal com perda neuronal e gliose.

A cross-sectional study to assess the association between major depression and inflammatory markers in patients with acute ischemic stroke.

BACKGROUND: Increased interest in the relationship between affective disorder and long-term health consequences has generated recent examinations of depression and stroke. Observations suggest that depressive disorder is associated with abnormal physiological and immunological responses and a resultant increase in inflammatory markers. Given the high prevalence of stroke and associated costs for the community, it is important to understand the mechanisms that may impact on the outcome to achieve the best possible prognosis. AIMS: The view that inflammatory factors contribute to depression is predicated on findings that circulating cytokines and other inflammatory factors are increased in depressed patients. Therefore, it has been hypothesized that inflammation could be one of the mechanisms by which depression increases risk for ischemic stroke. Our aim was to determine whether there is any relationship between major depression and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-18, brain-derived neurotrophic factor (BDNF), and neuron-specific enolase (NSE) in patients with acute ischemic stroke (AIS). STUDY DESIGN: This was as a cross-sectional design. MATERIALS AND METHODS: This study has a cross-sectional design, and it was conducted in Necmettin Erbakan University, the Meram Faculty of Medicine in Konya, Turkey, between 2014 and 2015. Fifty-three AIS patients admitted to the hospital within the first 24 h after stroke onset were recruited. Major depression was ascertained by means of the structured clinical interview for the diagnostic and statistical manual of mental disorders, Fourth Edition/Clinical Version. The enzyme-linked immunosorbent assay was used to measure the serum levels of TNF-α, IL-1 ß, IL-18, BDNF, and NSE at admission. RESULTS: A total of 53 patients with a mean age of 65.9 years were recruited. Of these patients, 17 (32.1%) had major depression. Depressive and nondepressive patients had similar demographical and clinical features. There was no significant statistical difference between depressive and nondepressive patients with AIS with respect to levels of TNF-α, IL-1 ß, IL-18, BDNF, and NSE. CONCLUSION: This study suggests that in patients who have experienced AIS, there is no significant relationship between major depression and basal proinflammatory cytokines (TNF-α, IL-1 ß, IL-18), BDNF, and NSE.

Clinical and radiologic features and their relationships with neurofunctional scores in patients with acute cerebellar infarct.

BACKGROUND: Cerebellar infarct is a rare condition with very nonspecific clinical features. The aim of this study was to assess the full spectrum of the clinical characteristics, neuroimaging findings and neurofunctional analyses of cerebellar infarction, and the relationship between them. MATERIALS AND METHODS: Data were collected from 59 patients admitted to our department during an 8-year period. We retrospectively analyzed the relationship between demographic characteristics, clinical symptomatology, etiological factors, functional condition, vascular distribution, frequency of subcortical white matter lesions (WMLs), and concomitant lesion outside the cerebellum in patients with acute cerebellar infarct (ACI) at time of admission. RESULTS: The mean age in our series was 65.2 years, with most being male (57.6%). The posterior inferior cerebellar (PICA) artery was the most commonly affected territory at 62.7%. There was concomitant lesion outside the cerebellum in 45.7%. The main etiology in PICA was cardioembolism. While mean National Institutes of Health Stroke Scale on admission was 2.08 ± 1.67 in study group, modified Rankin Scale (mRS) on admission was detected to be mRS1 (n: 44, 74.5%) and mRS2 (n: 12, 20.3%) most frequently. Fourteen (35%) patients were detected to be in Fazekas stage 0; 11 (27.5%) patients in Fazekas stage 1; 6 (15%) patients in Fazekas stage 2; and 9 (22.5%) patients in Fazekas stage 3. CONCLUSION: Cerebellar infarct is very heterogeneous. The other cerebral area infarcts which accompany ACI negatively affect neurologic functional scores. Although it is difficult to detect the relationship between WMLs and neurologic functional severity, timely detection of risk factors and their modulation may be associated with prevention and treatability of WMLs, and this may be one of the important points for prevention of stroke-related disability.

P-wave dispersion for predicting paroxysmal atrial fibrillation in acute ischemic stroke.

BACKGROUND: Detection of paroxysmal atrial fibrillation (PAF) in acute ischemic stroke patients poses diagnostic challenge. The aim of this study was to predict the presence of PAF by means of 12-lead ECG in patients with acute ischemic stroke. Our hypothesis was that P-wave dispersion (P(d)) might be a useful marker in predicting PAF in patients with acute ischemic stroke. METHODS: 12-lead resting ECGs, 24-hour Holter recordings and echocardiograms of 400 patients were analyzed retrospectively. PAF was detected in 40 patients on 24-hour Holter monitoring. Forty out of 360 age and gender matched patients without PAF were randomly chosen and assigned as the control group. Demographics, P-wave characteristics and echocardiographic findings of the patients with and without PAF were compared. RESULTS: Maximum P-wave duration (p=0.002), P(d) (p<0.001) and left atrium diameter (p=0.04) were significantly higher in patients with PAF when compared to patients without PAF. However, in binary logistic regression analysis P(d) was the only independent predictor of PAF. The cut-off value of P(d) for the detection of PAF was 57.5 milliseconds (msc). Area under the curve was 0.80 (p<0.001). On a single 12-lead ECG, a value higher than 57.5 msc predicted the presence of PAF with a sensitivity of 80% and a specificity of 73%. CONCLUSION: P(d) on a single 12-lead ECG obtained within 24 hours of an acute ischemic stroke might help to predict PAF and reduce the risk of recurrent strokes.

A Neuro-Behçet's Case Operated with the Intracranial Mass Misdiagnosis.

Behçet's disease (BD) is an inflammatory systemic disorder with oral and genital ulcers, as well as ophthalmologic and cutaneous symptoms. Neurological manifestations in BD represent between 2.2% to 50% of the cases. The 25-year-old male patient, diagnosed with BD three years earlier, was admitted to our clinic with complaints of recurrent headaches. Tumor-like-parenchimal involvement was detected on a cranial magnetic resonance imaging. The lesion was removed surgically and then he suffered from right hemiparesis and epilepsy. Pathological examination of the lesion noted a demyelinating non-tumoural etiology. A neuro-Behget's case with parenchymal involvement has been examined in light of the literature, in terms of a tumor and a demyelinating disease differential diagnosis.

Analysis of 24-hour heart rate variations in patients with epilepsy receiving antiepileptic drugs.

OBJECTIVE: The goal of the study described here was to evaluate interictal heart rate variability (HRV) in young patients with epilepsy, a patient population in whom sudden unexpected death in epilepsy (SUDEP) is known to be more common. METHODS: Twenty-four-hour ambulatory ECG Holter recordings of 37 patients (15-40 years old) and 32 healthy controls were compared. RESULTS: All of the time domain indices (SDNN, SDANN, RMSSD, and HRV triangular index) were significantly suppressed (P<0.001), and there was a marked reduction in parasympathetic tone (reduced HF(nu,)P<0.001) and an increase in sympathetic tone (increased LF(nu) and LF/HF ratio, P<0.001) in the patient group. Stepwise linear regression analysis revealed that polytherapy and epilepsy duration >10 years were independent variables associated with a reduction in SDNN. CONCLUSION: Our data suggest that the major determinants of suppressed SDNN are polytherapy and epilepsy duration >10 years. Analysis of spectral measures of frequency domain indices suggests that an increased sympathetic tone in association with a decreased parasympathetic tone may constitute the mechanism underlying SUDEP in young people with epilepsy.